THE ROLE OF ABCA8 IN THE BRAIN

Abstract

We found ABCA8 regulates myelination in the cerebellum, in part by interacting with and modulating CSPG4, a protein essential for oligodendrocyte precursor cell (OPC) proliferation, migration, and myelination. The absence of Abca8b, a mouse ortholog of ABCA8, led to reduced levels of cerebellar myelin, as well as Cnp, Plp1, and Mog, all essential myelin regulatory genes. Cerebellar myelin thickness and axonal diameter were decreased, indicating disordered myelin ultrastructure, whereas non-myelinated axon numbers were increased. In Abca8b-/- mice which showed lower cerebellar conduction velocity and disturbed locomotion, cerebellar size and weight, mature oligodendrocyte and OPC numbers, and cerebellar CSPG4 expression, as well as the plasma membrane localization of CSPG4 in OPCs, were decreased. Moreover, cerebellar CSPG4+ OPC numbers were reduced, likely leading to the observed decrease in myelinating OLs. We show that ABCA8 modulates myelination and may contribute to myelin disorders.